The present invention relates to novel sulfonamide compounds. More particularly, the present invention relates to novel sulfonamide compounds and salts thereof having hypoglycemic activity or PDE-V inhibitory activity. Moreover, the present invention relates to a method for producing the above-mentioned sulfonamide compound and salts thereof. The present invention also relates to pharmaceutical compositions comprising the above-mentioned sulfonamide compound or a salt thereof as an active ingredient.
The present invention aims at providing novel sulfonamide compounds, pharmaceutically acceptable salts thereof and pharmaceutical preparations comprising the above-mentioned sulfonamide compound or a pharmaceutically acceptable salt thereof as an active ingredient, which can be used for the prophylaxis and treatment of impaired glucose tolerance disorder, diabetes (e.g., type II diabetes), diabetic complications (e.g., diabetic gangrene, diabetic arthropathy, diabetic bone resorption, diabetic glomerulosclerosis, diabetic nephropathy, diabetic dermatopathy, diabetic neuropathy, diabetic cataract, diabetic retinopathy and the like), insulin resistant syndrome (e.g., insulin receptor disorders, Rabson-Mendenhall syndrome, leprechaunism, Kobberling-Dunnigan syndrome, Seip syndrome, Lawrence syndrome, Cushing syndrome, acromegaly and the like), polycystic ovary syndrome, hyperlipidemia, atherosclerosis, cardiovascular disorders (e.g., stenocardia, cardiac failure and the like), hyperglycemia (e.g., those characterized by abnormal saccharometabolism such as feeding disorders), hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy (e.g., diabetic glomerulosclerosis), tubulointerstitial disorders (e.g., kidney diseases induced by FK506, cyclosporine and the like), renal failure, angiostenosis (e.g., after percutaneous arterioplasty), distal angiopathy, cerebral apoplexy, chronic reversible obstructions (e.g., bronchitis, asthma inclusive of chronic asthma and allergic asthma), autoimmune diseases, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility (e.g., hypersensitive enteropathy), impotence (e.g., organic impotence, psychic impotence and the like), nephritis, cancer cachexia or restenosis after PTCA, pancreatitis, cachexia (e.g., progressive weight loss due to lipolysis, myolysis, anemia, edema, anorexia and the like in chronic diseases such as cancer, tuberculosis, endocrine diseases and AIDS), and the like.
The novel sulfonamide compound of the present invention has the following formula (I):
R1xe2x80x94SO2NHCOxe2x80x94Axe2x80x94Xxe2x80x94R2xe2x80x83xe2x80x83(I) 
wherein
R1 is an optionally substituted alkyl an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cyclo(lower)alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group;
A is an optionally substituted heteropolycyclic group except benzimidazolyl indolyl, 4,7-dihydrobenzimidazolyl and 2,3-dihydrobenzoxazinyl;
X is an alkylene, an ox an oxa(lower)alkylene, a lower alkyleneoxa, a carbonyl, a lower alkenylene, an optionally substituted imino, an optionally N-substituted imino(lower)alkylene, an optionally N-substituted lower alkyleneimino, a thioxa(lower)alkylene or a lower alkylenethioxa; and
R2 is an optionally substituted aryl an optionally substituted heterocyclic group or a substituted biphenylyl;
provided that when A is 3H-imidazo[4,5-b]pyridyl substituted by lower alkyl, R2 is an optionally substituted aryl, an optionally substituted heterocyclic group, or a biphenylyl substituted by a group other than tetrazolyl and when A is quinolyl substituted by lower alkyl, R2 is an optionally substituted aryl, an optionally substituted heterocyclic group, or a biphenylyl substituted by at least one group selected from the group consisting of all, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl other than substituted tetrazolylmethyl, halogen, amino, substituted amino, lower alkylsulfonyl lower alkylsulfinyl, lower alkylthio, cyano, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkoxy substituted by substituted amino, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycle-oxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group, (hereinafter also referred to as objective compound (I)).
Preferred salts of the objective compound (I) are conventional salts that are non-toxic and acceptable for use as pharmaceuticals. Examples thereof include salts of alkali metal such as sodium and potassium, salts of alkaline earth metal such as calcium and magnesium, salts with inorganic base such as ammonium salt, salts with organic amine such as triethylamine, pyridine, picoline, ethanolamine and triethanolamine, salts with inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, salts with organic carboxylic acid such as formic acid, acetic acid, tifluoroacetic acid, maleic acid and tartaric acid, addition salts with sulfonic acid such as methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid, addition salts with basic amino acid such as arginine, and addition salts with acidic amino acid such as aspartic acid and glutamic acid.
The objective compound (I) and a salt thereof can be produced by the method shown by the following reaction formula.
Production Method 1
wherein each symbol in the formula is as defined above.
The objective compound (I) and a salt thereof can be also produced by the methods shown by the following reaction formulas.
Production Method 2
wherein R201 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least alkynyl, aryl(lower)alkenyl, terminal nitro or terminal formyl, R202 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least alkyl, aryl(lower)alkyl, terminal amino or hydroxymethyl, and other symbols are as defined above.
Production Method 3
wherein R203 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least terminal formyl, R204 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least carboxy, and other symbols are as defined above.
Production Method 4 
wherein a is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl all of which having at least hydroxy(lower)alkyl, R206 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least acyloxy(lower)alkyl, and other symbols are as defined above.
Production Method 5 
wherein R207 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl all of which having at least aryloxy(lower)alkyl, and other symbols are as defined above.
Production Method 6 
wherein R208 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least protected carboxy, and other symbols are as defined above.
Production Method 7 
wherein R209 is an optionally substituted aryl, an optionally substituted heterocyclic group or a substituted biphenylyl, all of which having at least optionally substituted amide, and other symbols are as defined above.
Production Method 8 
wherein R210 is an optionally substituted aryl having at least a halogen atom, 
is a heterocyclic group having nitrogen, R211 is an aryl substituted by at least heterocyclic group having nitrogen, and other symbols are as defined above.
Various definitions included in the entire specification are explained in detail in the following.
xe2x80x9cLowerxe2x80x9d means 1 to 6 carbon atoms, unless otherwise specified.
xe2x80x9cHigherxe2x80x9d means 7 to 20 carbon atoms, unless otherwise specified.
xe2x80x9cAlkylxe2x80x9d and xe2x80x9calkyl moietyxe2x80x9d are preferably linear or branched lower alkyl and higher alkyl, respectively. Specific examples include methyl, ethyl n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, sec-butyl, n-pentyl, i-pentyl, sec-pentyl, t-pentyl, methylbutyl, 1,1-dimethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1imethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1-ethyl-1-methylpropyl, n-heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-ethylpentyl, 2-ethylpentyl, 3-ethylpentyl, 4-ethylpentyl, 1,1-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 4,4-dimethylpentyl, 1-propylbutyl, n-octyl, 1-methylheptyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1-ethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 5-ethylhexyl, 5ethylhexyl, 1,1-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl 5,5-dimethylhexyl, 1-propylpentyl, 1-propylpentyl and the like.
Of these, particularly preferred is alkyl having 2 to 8 carbon atoms.
xe2x80x9cAlkenylxe2x80x9d and xe2x80x9clower alkenyl moietyxe2x80x9d are preferably exemplified by linear or branched lower alkenyl and higher alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like.
Of these, particularly preferred is alkenyl having 2 to 8 carbon atoms.
xe2x80x9cAlkynylxe2x80x9d is preferably a linear or branched lower alkynyl or higher alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-methyl-3-butynyl, 1,1-dimethyl-2-butynyl, 1-hexynyl, 5-hexynyl, and the like.
Of these, particularly preferred is alkyl having 2 to 8 carbon atoms.
xe2x80x9cCyclo(lower)alkylxe2x80x9d is cycloalkyl having 3 to 10, preferably 3 to 7, carbon atoms. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, with preference given to cyclopropyl, cyclobutyl and cyclohexyl.
Examples of preferable aryl include aryl having 6 to 10 carbon atoms, such as phenyl, naphthyl and pentalenyl.
Of these, particularly preferred are phenyl and naphthyl.
xe2x80x9cHeterocyclic groupxe2x80x9d is a saturated or unsaturated, heteromonocyclic or heteropolycyclic group having at least one hetero atom, such as oxygen atom, sulfur atom, nitrogen atom and selenium atom. Particular, heteropolycyclic group (specifically heterobicyclic group) and unsaturated 3- to 8-membered heteromonocyclic group having 1 or 2 sulfur atom(s) are preferable.
Preferred heterocyclic group includes the following.
Heteromonocyclic group includes the following.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 to 4 nitrogen atoms, such as pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl and 2H-1,2,3-triazolyl), tetrazolyl (e.g., 1H-tetrazolyl and 2H-tetrazolyl) and the like.
Saturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 to 4 nitrogen atoms, such as pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 or 2 oxygen atoms and 1 to 3 nitrogen atoms, such as oxazolyl, isooxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl and 1,2,5-oxadiazolyl) and the like.
Saturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic having 1 or 2 oxygen atoms and 1 to 3 nitrogen atoms, such as morpholinyl, sydnonyl and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 or 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolyl, isothiazolyl, thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl and 1,2,5-thiadiazolyl), dihydrothiazinyl and the like.
Saturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 or 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolidinyl and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 or 2 sulfur atoms, such as thienyl, dihydrodithiinyl, dihydrodithionyl and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having 1 or 2 oxygen atoms, such as tetrahydrofuryl, tetrahydropyranyl and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having one oxygen atom, such as furyl and the like.
Spiroheterocyclic group having 1 or 2 oxygen atoms, such as dioxaspiroundecanyl (e.g., 1,5-dioxaspiro[5,5]undecanyl) and the like.
Unsaturated 3 to 8-membered (more preferably 5- or 6-membered) heteromonocyclic group having one oxygen atom and 1 or 2 sulfur atoms, such as dihydroxathinyl.
Examples of heteropolycyclic group include the following.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 to 4 nitrogen atoms, exclusive of benzimidazolyl and indolyl.
Specific examples thereof include 2,3-dihydrobenzimidazolyl, pyrazolopyprimidinyl a (e.g., pyrazolo[1,5-a]pyrimidinyl), tetrahydropyrazolopyrimidinyl (e.g., 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidinyl), imidazopyrazolyl (e.g., 4H-imidazo[1,2-b]pyrazolyl), dihydroimidazopyrazolyl (e.g., 2,3-dihydroimidazo[1,2-b]pyrazolyl), imidazopyridyl (e.g., imidazo[1,5-a] (or [1,2-a] or [3,4-a])pyridyl, 1H (or 3H-imidazo[4,5-b] (or [4,5-c])pyridyl), pyrazolopyridyl (e.g., 1H-pyrrolo[3,2-b]pyridyl), pyrazolopyridyl (e.g., pyrazolo[1,5-a] (or [2,3-a]pyridyl, 1H (or 2H)-pyrazolo[4,3-b]pyridyl), benzopyrazolyl (e.g., 1H (or 2H)-benzo[c]pyrazolyl), dihydrobenzimidazolyl, benzotriazolyl (e.g., benzo[d][1H-1,2,3]triazolyl, indolizinyl, isoindolyl (e.g., 1H-isoindolyl), indazolyl (e.g., 1H (or 2H or 3H)-indazolyl), indolinyl, isoindolinyl, purinyl, quinolizinyl (e.g., 4H-quinolizinyl), isoquinolyl, quinolyl, phthalazinyl, naphthalidinyl (e.g., 1,8-naphthalidinyl), quinoxalinyl, dihydroquinoxalinyl (e.g., 1,2-dihydroquinoxalinyl, tetrahydroquinoxalinyl (e.g., 1,2,3,4-tetrahydroquinoxalinyl), quinazolinyl, dihydroquinazolinyl (e.g., 1,4 (or 3, 4)-dihydroquinazolinyl), tetrahydroquinazolinyl (e.g., 1,2,3,4-tetrahydroquinazolinyl), cinnolinyl, pteridinyl, pyrazinopyridazinyl (e.g., pyrazino[2,3-d]pyridazinyl), imidazotriazinyl (e.g., imidazo[1,2-b][1,2,4]triazinyl, imidazopyrazinyl (e.g., 1H-imidazo[4,5-b]pyrazinyl), imidazopyrimidine (e.g., 3H-purine and imidazo[1,5-a] (or [3,4-a])pyrimidine), imidazopidazinyl (e.g., imidazo[2,3-b] (or [3,4-b])pyridazinyl), 1H-1-(or 2)pyrinedinyl and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 to 3 oxygen atoms.
Specific examples thereof include benzofuranyl (e.g., benzo[b] (or [c])furanyl), isobenzofuranyl, furopyridyl, chromenyl (e.g., 2H-chromenyl), chromanyl, isochromanyl, benzoxepinyl (e.g., 3-benzoxepinyl), cyclopentapyranyl (e.g., cyclopenta[b]pyranyl), furopyranyl (e.g., 2H-furo[3,2-b]pyranyl), and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 to 3 sulfur atoms.
Specific examples thereof include benzothiophenyl (e.g., benzo[b]thiophenyl), dihydrodithiaphthalenyl (e.g., 4H-1,3-dithiaphthalenyl), dithianaphthalenyl (e.g., 1,4-dithlanaphthalenyl) and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10membered) heteropolycyclic (more preferably heterodicyclic) group having 1 to 3 nitrogen atoms and 1 or 2 oxygen atoms.
Specific examples thereof include dioxoloimidazolyl (e.g., 4H-1,3-dioxolo[4,5-d]imidazolyl, benzoxazinyl (e.g., 4H-3,1-benzoxazinyl), pyridooxazinyl (e.g., 5H-pyrido[2,3-d]oxazinyl), pyrazolooxazolyl (e.g., 1H-pyrazolo[4,3-d]oxazolyl), furopyridyl, and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycylic (more preferably heterodicyclic) group having 1 to 3 nitrogen atoms and 1 or 2 sulfur atoms.
Specific examples thereof include thienoimidazolyl (e.g., thieno[2,3-d]imidazolyl), thienopyridyl, ditiadiazaindanyl (e.g., 2,3-dithia-1,5-diazaindanyl) and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 to 3 oxygen atoms and 1 or 2 sulfur atoms.
Specific examples thereof include thienofuranyl (e.g., thieno[2,3-b]furanyl), and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 nitrogen atom, 1 oxygen atom and 1 sulfur atom.
Specific examples thereof include oxathiolopyrrolyl (e.g., 4H[1,3]-oxathiolo[5,4-b]pyrrolyl, and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 or 2 selenium atoms.
Specific examples thereof include benzoselenophenyl (e.g., benzo[b] (or [c])selenophenyl), and the like.
Saturated or unsaturated 7 to 12-membered (more preferably 8 to 10-membered) heteropolycyclic (more preferably heterodicyclic) group having 1 or 2 selenium atoms and 1 to 3 nitrogen atoms.
Specific examples thereof include selenopyridyl (e.g., seleno[3,2-b]pyridyl), and the like.
Examples of preferable lower alkylene include methylene, ethylene, propylene, butylene, pentylene, hexylene and the like, with preference given to alkylene having up to 4 carbon atoms.
Examples of preferable lower alkenylene include ethenylene, 1-propenylene, 2-propenylene, 1-butenylene, 2-butenylene, 3-butenylene, 1-pentenylene, 2-pentenylene, 3-pentenylene, 4-pentenylene, 1-hexenylene, 2-hexenylene, 3-hexenylene, 4-hexenylene, 5-hexenylene and the like, with preference given to alkenylene having up to 4 carbon atoms.
The lower alkylene moiety of oxa(lower)alkylene, lower alkyleneoxa, imino(lower)alkylene, lower alkyleneimino, thioxa(lower)alkylene and lower alkylenethioxa is the same as that of the above-mentioned alkylene.
Lower alkanoyl is a linear or branched alkylcarbonyl having up to 6 carbon atoms. Examples thereof include acetyl, propionyl, n-butyryl, isobutyryl, valeryl, isovaleryl, sec-butylcarbonyl, t-butylcarbonyl, n-pentylcarbonyl, i-pentylcarbonyl, sec-pentylcarbonyl, t-pentylcarbonyl, 2-methylbutylcarbonyl and the like.
More preferred is alkanoyl having up to 4 carbon atoms.
Lower alkoxy is a linear or branched alkyloxy having up to 6 carbon atoms. Examples thereof include methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, sec-butyloxy, t-butyloxy, n-pentyloxy, i-pentyloxy, sec-pentyloxy, t-pentyloxy, 2-methylbutoxy, n-hexyloxy, i-hexyloxy, t-hexyloxy, sec-hexyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 1-ethylbutyloxy, 2-ethylbutyloxy, 1,1-dimethylbutyloxy, 2,2-dimethylbutyloxy, 3,3-dimethylbutyloxy, 1-ethyl-1-methylpropyloxy, and the like.
More preferred is alkoxy having up to 4 carbon atoms, such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, sec-butyloxy, t-butyloxy, and the like.
Heterocycle(lower)alkyl means lower a substituted by the above-mentioned heterocyclic group.
Halogen is exemplified by fluorine atom, chlorine atom, bromine atom and iodine atom.
The substituted amino of xe2x80x9csubstituted aminoxe2x80x9d and xe2x80x9coptionally substituted aminoxe2x80x9d is, for example, lower alkanoylamino, mono(lower)alkylamino, di(lower)alkylamino, N-(lower)alkyl-N-acylamino, lower alkylsulfonylamino, aryl(lower)alkylamino, N-heterocycle-N-(lower)alkylamino, arylsulfonylamino, arylcarbonylamino and the like. Examples of N-(lower)alkyl-N-acylamino include N-(lower)alkyl-N-(arylcarbonyl)amino and the like.
xe2x80x9cLower alkanoylaminoxe2x80x9d is amino substituted by the above-mentioned lower alkanoyl.
xe2x80x9cMono or di(lower)alklaminoxe2x80x9d is amino substituted by linear or branched alkyl having up to 6 carbon atoms. Examples thereof include methylamino, ethylamino, n-propylamino, i-propylamino, n-butylamino, i-butylamino, sec-butylamino, t-butylamino, n-pentylamino, i-pentylamino, sec-pentylamino, t-pentylamino, 2-methylbutylamino, n-hexylamino, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 1-ethylbutylamino, 2-ethylbutylamino, 3-ethylbutylamino, 1,1-dimethylbutylamino, 2,2-dimethylbutylamino, 3,3-dimethylbutylamino, 1-ethyl-1-methylpropylamino and the like.
Preferred is alkylamino having up to 4 carbon atoms, such as methylamino, ethylamino, n-propylamino, i-propylamino, n-butylamino, i-butylamino, sec-butylamino, t-butylamino and the like.
Preferable xe2x80x9cacylxe2x80x9d in xe2x80x9cN-(lower)alkyl-N-acylaminoxe2x80x9d is exemplified by carbamoyl, aliphatic acyl, aromatic acyl, and acyl having a heterocycle, such as heterocyclic acyl.
Examples of the above-mentioned acyl include carbamoyl; lower or higher (having not less than 7, preferably 7 to 25, carbon atoms) alkanoyl, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, icosanoyl and the like; lower or higher alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl, heptyloxycarbonyl and the like; lower or higher alkanesulfonyl, such as methanesulfonyl, ethanesulfonyl and the like; aliphatic acyl such as lower or higher alkoxysulfonyl (e.g., methoxysulfonyl and ethoxysulfonyl); aroyl such as benzoyl, toluoyl, naphthoyl and the like; phenyl(lower)alkanoyl, such as phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutyryl, phenylpentanoyl, phenylhexanoyl and the like and aryl(lower)alkanoyl (e.g., naphthyl(lower)alkanoyl such as naphthylacetyl, naphthylpropanoyl and naphthylbutanoyl); phenyl(lower)alkenoyl such as phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentenoyl, phenylhexenoyl and the like and aryl(lower)alkenoyl such as naphthyl(lower)alkenoyl (e.g., naphthyl propenoyl, naphthyl butenoyl and naphthyl pentenoyl); aryl(lower)alkoxycarbonyl such as phenyl(lower)alkoxycarbonyl (e.g., benzyloxycarbonyl); aryloxycarbonyl such as phenoxycarbonyl, naphthyloxycarbonyl and the like; aryloxy(lower)alkanoyl such as phenoxyacetyl, phenoxypropionyl and the like; arylcarbamoyl such as phenylcarbamoyl and the like; arylthiocarbamoyl such as phenylthiocarbamoyl and the like; arylglyoxyloyl such as phenylglyoxyloyl, naphthylglyoxyloyl and the like; aromatic acyl such as arenesulfonyl (e.g., benzenesulfonyl and p-toluenesulfonyl); heterocyclecarbonyl; heterocyle(lower)alkanoyl such as thienylacetyl, thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, tetrazolylacetyl and the like; heterocycle(lower)alkenoyl such as heterocycle propenoyl, heterocyclebutenoyl, heterocyclepentenoyl, heterocyclehexenoyl and the like; heterocycleglyoxyloyl such as thiazolylglyoxyloyl, thienylglyoxyloyl and the like.
The preferable heterocycle moiety of the above-mentioned xe2x80x9cheterocycle carbonylxe2x80x9d, xe2x80x9cheterocycle(lower)alkanoylxe2x80x9d, xe2x80x9cheterocycle(lower)alkenoylxe2x80x9d and xe2x80x9cheterocycleglyoxyloylxe2x80x9d is a saturated or unsaturated heteromonocyclic or heteropolycyclic group having at least one hetero atom such as oxygen atom, sulfur atom, nitrogen atom and the like, with preference given to the heterocyclic groups mentioned above.
The aforementioned acyl moiety may have 1 to 10 same or different suitable substituent(s), such as halogen (e.g., fluorine, chlorine, bromine and iodine), hydroxy, nitro, lower alkyl (e.g., methyl, ethyl, propyl, isopropyl butyl, isobutyl, t-butyl, pentyl and hexyl), amino, protected amino, heterocycle(lower)alkylamino having the above-mentioned heterocycle moiety and lower alkyl moiety, lower alkoxy (e.g., methoxy, ethoxy, propoxy, butyloxy, t-butyloxy, pentyloxy and hexyloxy), carboxy, protected carboxy, N,N-di(lower)alkylamino(lower)alkyl (e.g., N,N-dimethylaminomethyl, N,N-diethylaminoethyl, N,N-dipropylaminomethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dipropylaminoethyl, N,N-dimethylaminopropyl, N,N-diethylaminopropyl, N,N-dipropylaminopropyl, N,N-dibutylaminomethyl, N,N-dipentylaminomethyl and N,N-dihexylamiomethyl), hydroxyimino (lower)alkyl (e.g., hydroxyiminomethyl, hydroxyiminoethyl, hydroxyiminopropyl, hydroxyiminobutyl, hydroxyiminopentyl and hydroxyiminohexyl), arylimino(lower)alkyl such as phenylimino(lower)alkyl (e.g., phenyliminomethyl, phenyliminoethyl, phenyliminopropyl, phenyliminobutyl, phenyliminopentyl and phenyliminohexyl), acyl such as lower alkanoyl (e.g., formyl, acetyl, propanoyl, butanoyl, pentanoyl and hexanoyl), hydroxy(lower)alkylheterocycle(lower)alkyl having the above-mentioned lower alkyl moiety and heterocyclic moiety, mono-(or di- or tri-)halo(lower)alkyl, arylamino (e.g., phenylamino) and the like.
xe2x80x9cLower alkylsulfonylxe2x80x9d and xe2x80x9clower alkylsulfinylxe2x80x9d are sulfonyl and sulfinyl respectively substituted by the above-mentioned lower alkyl.
xe2x80x9cLower alkylthioxe2x80x9d is a linear or branched alkylthio having up to 6 carbon atoms. Examples thereof include methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio, i-butylthio, sec-butylthio, t-butylthio, n-pentylthio, i-pentylthio, sec-pentylthio, t-pentylthio, 2-methylbutylthio, n-hexylthio, i-hexylthio, t-hexylthio, sec-hexylthio, 2-methylpentylthio, 3-methylpentylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1-dimethylbutylthio, 2,2-dimethylbutylthio, 3,3-dimethylbutylthio, 1-ethyl-1-methylpropylthio and the like.
More preferred is alkylthio having up to 4 carbon atoms, such as methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio, i-butylthio, sec-butylthio, t-butylthio and the like.
xe2x80x9cMono- or di(lower)alklylcarbamoylxe2x80x9d is carbamoyl mono- or di-substituted by the above-mentioned lower alkyl.
xe2x80x9cHalo(lower)alklylxe2x80x9d is a linear or branched alkyl having up to 6 carbon atoms, which is substituted by fluorine atom, chlorine atom, bromine atom or iodine atom, and is preferably exemplified by a linear or branched awl having up to 6 carbon atoms, which is substituted by fluorine atom, chlorine atom or bromine atom. Examples thereof include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1,2-difluoroethyl, 1,2-dichloroethyl, 1,2-dibromoethyl, 2,2,2-trifluoroethyl, heptafluoroethyl, 1-fluoropropyl, 1-choropropyl, 1-bromopropyl, 2-fluoropropyl, 2-choropropyl, 2-bromopropyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 1,2-difluoropropyl, 1,2-dichloropropyl, 1,2-dibromopropyl, 2,3-difuoropropyl, 2,3-dichloropropyl, 2,3-dibromopropyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-penta fluoropropyl, 2-fluorobutyl, 2-chlorobutyl, 2-bromobutyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, 4,4,4-trifluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, perfluorobutyl, 2-fluoropentyl, 2-chloropentyl, 2-bromopentyl, 5-fluoropentyl, 5-chloropentyl, 5-bromopentyl, perfluoropentyl, 2-fluorohexyl, 2-chlorohexyl, 2-bromohexyl, 6-fluorohexyl, 6-chlorohexyl, 6-bromohexyl, perfluorohexyl, 2-fluoroheptyl, 2-chloroheptyl, 2-bromoheptyl, 7-fluoroheptyl, 7-fluoroheptyl, 7-chloroheptyl, 7-bromoheptyl, perfluoroheptyl and the like.
Examples of preferable aryl(lower)alkyl include C6-C10aryl(C1-C6)alkyl such as benzyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, naphthylmethyl, naphthylethyl, naphthylpropyl, naphthylbutyl, naphthylpentyl, naphthylhexyl and the like.
xe2x80x9cAryl(lower)alkenylxe2x80x9d and xe2x80x9caryl(lower)alkoxy,xe2x80x9d are respectively the above-mentioned lower alkenyl and lower alkoxy substituted by the above-mentioned aryl.
xe2x80x9cProtected carboxyxe2x80x9d is preferably esterified carboxy.
Examples of preferable ester moiety of the esterified carboxy include lower alkyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, t-butyl ester, pentyl ester and hexyl ester. These groups may have at least one appropriate substituent, which is exemplified by (lower)alkanoyloxy-(lower)alkyl ester such as acetoxymethyl ester, propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1 (or 2)-acetoxyethyl ester, 1 (or 2 or 3)-acetoxypropyl ester, 1 (or 2 or 3 or 4)-acetoxybutyl ester, 1 (or 2)-propionyloxyethyl ester, 1 (or 2 or 3)-propionyloxypropyl ester, 1 (or 2)-butyryloxyethyl ester, 1 (or 2)-isobutyryloxyethyl ester, 1 (or 2)-pivaloyloxyethyl ester, 1 (or 2)-hexanoyloxyethyl ester, isobutyryloxy-methyl ester, 2-ethylbutyryloxymethyl ester, 3,3-dimethylbutyryloxmethyl ester, 1 (or 2)-pentanoyloxyethyl ester), and the like, lower alknesulfonyl(lower)alkyl ester (e.g., 2-mesylethyl ester), mono-(or di- or tri)halo(lower)alkyl ester (e.g., 2-iodoethyl ester and 2,2,2-trichloroethyl ester), lower alkoxycarbonyloxy(lower)alkyl ester (e.g., methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, 2-methoxy-carbonyloxyethyl ester, 1-ethoxycarbonyloxyethyl ester and 1-isopropoxycarbonyl-oxyethyl ester), phthalidylidene(lower)alkyl ester and (5-(lower)alkyl-2-oxo-1,3-dioxol4-yl(lower)alkyl ester (e.g., (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester, (5-ethyl-2-oxo-1,3-dioxol-4-yl)methyl ester and (5-propyl-2-oxo-1,3-dioxol-4-yl)ethyl ester); lower alkenyl ester (e.g., vinyl ester and allyl ester); lower alkenyl ester (e.g., ethynyl ester and propynyl ester); aryl(lower)alkyl ester optionally having at least one suitable substituent, such as mono-(or di- or tri-)phenyl(lower)alkyl ester optionally having at least one suitable substituent, which is exemplified by benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenylethyl ester, trityl ester, benzhydryl ester, bis(methoxyphenyl)methyl ester, 3,4-dimethoxybenzyl ester and 4-hydroxy-3,5-di-t-butylbenzyl ester, aryl ester optionally having at least one suitable substituent, such as phenyl ester, 4-chlorophenyl ester, tolyl ester, t-butylphenyl ester, xylyl ester, mesityl ester and cumenyl ester, cyclo(lower)alkyl ester (e.g., cyclohexyl ester); phthalidyl ester, and the like.
The heterocyclic group having nitrogen, which is represented by 
is exemplified by the above-mentioned heterocyclic group having nitrogen.
The preferable objective compound (I) is a compound of the formula (I) having the following groups and pharmaceutically acceptable salts thereof. R1 is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cyclo(lower)alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group, wherein, when the above groups are substituted, the substituent is at least one member selected from the group consisting of alklyl, cyclo(lower)alkyl, alkenyl alkynyl, lower alkanoyl, lower alkoxy, aryl, heterocycle(lower)alkyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkoxy substituted by substituted amino, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl-(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycleoxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group. A is a heteropolycyclic group having at least one hetero atom, such as oxygen atom, sulfur atom, selenium atom and nitrogen atom, exclusive of benzimidazolyl, indolyl, 4,7-dihydrobenzimidazolyl and 2,3-dihydrobenzoxazinyl, said heterocyclic group being optionally substituted by at least one member selected from the group consisting of alkyl, oxo, thioxo, halogen, lower alkoxy, lower alkylthio, cyclo(lower)alkyl, optionally substituted amino, aryl, heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl. R2 is optionally substituted aryl optionally substituted heterocyclic group or substituted biphenylyl, wherein, when these groups are substituted, the substituent is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, aryl, heterocycle(lower)alkyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkoxy substituted by substituted amino, cyclo(lower)alkyl-(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy-(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycleoxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group,
provided that when A is 3H-imidazo[4,5-b]pyridyl substituted by lower alkyl, R2 is optionally substituted aryl optionally substituted heterocyclic group or biphenylyl substituted by a substituent other than tetrazolyl, and when A is quinolyl substituted by lower alkyl, R2 is optionally substituted aryl, optionally substituted heterocyclic group or substituted biphenylyl.
When the above-mentioned aryl and heterocyclic group are substituted, the substituent is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkoxy substituted by substituted amino, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycle-oxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group.
The substituent for the above-mentioned biphenylyl is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl other than substituted tetrazolylmethyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkoxy substituted by substituted amino, cyclo(lower)alkyl-(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy-(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycle-oxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group.
Of the above-mentioned compounds, a compound of the formula (I) having the following and pharmaceutically acceptable salts thereof are particularly preferable. R1 is an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cyclo(lower)alkyl, an optionally substituted phenyl or an optionally substituted heterocyclic group, wherein, when these groups are substituted, the substituent is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl, halogen, amino, lower alkanoylamino, mono(lower)alkylamino, di(lower)alkylamino, N-(lower)alkyl-N-acylamino, lower alkylsulfonylamino, aryl(lower)alkylamino, N-heterocycle-N-(lower)alkylamino, arylsulfonylamino, arylcarbonylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkanoylamino(lower)alkoxy, mono(lower)alkylamino(lower)alkoxy, di(lower)alkylamino(lower)alkoxy, N-(lower)alkyl-N-acylamino(lower)alkoxy, lower alkylsulfonylamino(lower)alkoxy, aryl(lower)alkylamino(lower)alkoxy, N-heterocycle-N-(lower)alkylamino(lower)alkoxy, arylsulfonylamino(lower)alkoxy, arylcarbonylamino(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycle lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group. substituted divalent heterocyclic group and potionally substituted heterocyclic group. A is a heterocyclic group of the following (A) to (I) exclusive of benzimidazolyl, indolyl, 4,7-dihydrobenzimidazolyl and 2,3-dihydrobenzoxazinyl, wherein said heterocyclic group may be substituted by at least one member selected from the group consisting of alkyl, oxo, thioxo, halogen, lower alkoxy, lower alkylthio, cyclo(lower)alkyl, amino, lower alkanoylamino, mono(lower)alkylamino, di lower)alkylamino, N-lower)alkyl-N-acylamino, lower alkylsulfonylamino, aryl(lower)alkylamino, N-heterocycle-N-(lower)alkylamino, arylsulfonylamino, arylcarbonylamino, heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl,
provided that when A is 3H-imidazo[4,5-b]pyridyl substituted by lower alkyl, R2 is an optionally substituted aryl, optionally substituted heterocyclic group or biphenylyl substituted by a group other than tetrazolyl, and when A is quinolyl substituted by lower alkyl, R2 is an optionally substituted phenyl, optionally substituted naphthyl, optionally substituted heterocyclic group or substituted biphenylyl.
The substituent for the above-mentioned phenyl, naphthyl and heterocyclic group is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl, halogen, amino, lower alkanoylamino, mono(lower)-alkylamino, di(lower)alkylamino, N-(lower)alkyl-N-acylamino, lower alkylsulfonyl-amino, aryl(lower)alkylamino, N-heterocycle-N-(lower)alkylamino, arylsulfonylamino, arylcarbonylamino, lower alkylsulfonyl, lower alkysulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkyl-carbamoyl, nitro, halo(lower)alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)-alkoxy, lower alkanoylamino(lower)alkoxy, mono(lower)alkylamino, di(lower)alkylamino(lower)alkoxy, N-(lower)alkyl-N-acylamino(lower)alkoxy, lower alkylsulfonylamino(lower)alkoxy, aryl(lower)alkylamino(lower)alkoxy, N-heterocycle-N-(lower)alkylamino(lower)alkoxy, arylsulfonylamino(lower)alkoxy, arylcarbonyl-amino(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkyl-amino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle-(lower)alkoxy, heterocycle-oxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group.
The substituent for the above-mentioned biphenylyl is at least one member selected from the group consisting of alkyl, cyclo(lower)alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocycle(lower)alkyl other than substituted tetrazolylmethyl, halogen, amino, lower alkanoylamino, mono(lower)alkylamino, di(lower)alkylamino, N-(lower)alkyl-N-acylamino, lower alkylsulfonylamino, aryl(lower)alkylamino, N-heterocycle-N-(lower)alkylamino, arylsulfonylamino, arylcarbonylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carbamoyl, mono(lower)alkylcarbamoyl, di(lower)alkylcarbamoyl, nitro, halo(lower)-alkyl, aryl(lower)alkyl, aryl(lower)alkenyl, aryl(lower)alkoxy, lower alkanoylamino-(lower)alkoxy, mono(lower)alkylamino(lower)alkoxy, di(lower)alkylamino(lower)alkoxy, N-(lower)alkyl-N-acylamino(lower)alkoxy, lower alkylsulfonylamino(lower)alkoxy, aryl(lower)alkylamino(lower)alkoxy, N-heterocycle-N-(lower)alkyl(lower)alkoxy, arylsulfonylamino(lower)alkoxy, arylcarbonylamino(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, aryloxy(lower)alkyl, acyloxy(lower)alkyl, hydroxy(lower)alkyl, mono- or di(lower)alkylamino(lower)alkyl, aryl(lower)alkoxy(lower)alkyl, arylthio(lower)alkyl, heterocycle(lower)alkoxy, heterocycle-oxy(lower)alkyl, aryl(lower)alkylthio, arylureido, lower alkoxy(lower)alkoxy, aryl(lower)alkynyl, lower alkyl substituted by optionally substituted divalent heterocyclic group and optionally substituted heterocyclic group.
The above-mentioned heterocyclic group means the following (A) to (T):
(A) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 to 4 nitrogen atoms
(B) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 to 3 oxygen atoms
(C) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 to 3 sulfur atoms
(D) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 to 3 nitrogen atoms and 1 or 2 oxygen atoms
(E) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 to 3 nitrogen atoms and 1 or 2 sulfur atoms
(F) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 or 2 oxygen atoms and 1 or 2 sulfur atoms
(G) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 nitrogen atom, 1 oxygen atom and 1 sulfur atom
(H) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 or 2 selenium atoms
(I) saturated or unsaturated 7 to 12-membered heterobicyclic group having 1 or 2 selenium atoms and 1 to 3 nitrogen atoms
(J) unsaturated 3 to 8-membered heteromonocyclic group having 1 to 4 nitrogen atoms
(K) saturated 3 to 8-membered heteromonocyclic group having 1 to 4 nitrogen atoms
(L) unsaturated 3 to 8-membered heteromonocyclic group having 1 or 2 oxygen atoms and 1 to 3 nitrogen atoms
(M) saturated 3 to 8-membered heteromonocyclic group having 1 or 2 oxygen atoms and 1 to 3 nitrogen atoms
(N) unsaturated 3 to 8-membered heteromonocyclic group having 1 or 2 sulfur atoms and 1 to 3 nitrogen atoms
(O) saturated 3 to 8-membered heteromonocyclic group having 1 or 2 sulfur atoms and 1 to 3 nitrogen atoms
(P) unsaturated 3 to 8-membered heteromonocyclic group having 1 or 2 sulfur atoms
(Q) unsaturated 3 to 8-membered heteromonocyclic group having 1 or 2 oxygen atoms
(R) unsaturated 3 to 8-membered heteromonocyclic group having 1 oxygen atom
(S) spiroheterocyclic group having 1 or 2 oxygen atoms
(T) unsaturated 3 to 8-membered heteromonocyclic group having 1 oxygen atom and 1 or 2 sulfur atoms
Of the above-mentioned compounds, a compound of the formula (I) wherein A is a heterocyclic group selected from the group consisting of 2,3-dihydrobenzimidazolyl, pyrazolopyrimidinyl, tetrahydropyrazolopyrimidinyl, imidazopyrazolyl, dihydroimidazopyrazolyl, imidazopyridyl, pyrrolopyridyl, pyrazolopyridyl, benzopyrazolyl, dihydrobenzimidazolyl, benzotriazolyl, indolizinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthalidinyl, quinoxalinyl, dihydroquinoxalinyl, tetrahydroquinoxalinyl, quinazolinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, cinnolinyl, pteridinyl, pyrazinopyridazinyl, imidazotriazinyl, imidazopyrazinyl, imidazopyrimidinyl, imidazopyridazinyl, 1H-1-(or 2)pyridazinyl, benzofuranyl, isobenzofuranyl, furopyridyl, chromenyl, chromanyl, isochromanyl, benzoxepinyl, cyclopentapyranyl, furopyranyl, benzothiophenyl, dihydrodithianaphthalenyl, dithianaphthalenyl, dioxoloimidazolyl, benzoxazinyl, pyridoxazinyl, pyrazolooxazolyl, furopyridyl, thienoimidazolyl, thienopyridyl, dithiadiazaindanyl, thienofuranyl, oxathiolopyrrolyl, benzoselenophenyl, selenopyridyl, benzoselenol, selenopyridyl and cyclopentadienopyridyl. These heterocyclic groups are preferably optionally substituted by lower ally and/or oxo.
Of the above-mentioned compounds, preferably exemplified is a compound of the formula (I) wherein R1 is an alkyl, an alkenyl, a phenyl(lower)alkenyl, a quinolyl, a phenyl optionally substituted by a substituent selected from the group consisting of nitro, alkyl and alkenyl, or a thienyl optionally substituted by halogen; A is a heterocyclic group selected from the group consisting of 2,3-dihydrobenzimidazolyl, imidazopyrazolyl, imidazopyridyl, pyrrolopyridyl, pyrazolopyridyl, benzotriazolyl, indolizinyl, indazolyl, quinolyl, dihydroquinoxalinyl, tethydroquinoxalinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, benzofuranyl, benzothiophenyl and thienoimidazolyl, said heterocyclic group being optionally substituted by alkyl or oxo; X is a lower alkylene, an oxa(lower)alkylene or an oxa; and R2 is a phenyl optionally substituted by a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, imidazolyl(lower)alkyl, piperidinyl-(lower)alkyl, halogen, amino, lower alkanoylamino, mono(lower)alkylamino, di(lower)alkylamino, N-(lower)alkyl-N-(lower)alkanoylamino, N-(lower)alkyl-N-benzoylamino, lower alkylsulfonylamino, phenyl(lower)alkylamino, phenyl-sulfonylamino, benzoylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, lower alkoxycarbonyl, cyclo(lower)alkyloxycarbonyl, mono(lower)-alkylcarbamoyl, nitro, halo(lower)alkyl, phenyl(lower)alkyl, phenyl(lower)alkenyl, phenyl(lower)alkoxy, (N-pyridyl-N-(lower)alkylamino(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkyl, phenoxy(lower)alkyl, lower alkylsulfonyloxy(lower)alkyl, hydroxy(lower)alkyl, di(lower)alkylamino-(lower)alkyl, phenyl(lower)alkoxy(lower)alkyl, phenylthio(lower)alkyl, thienyl(lower)-alkoxy, pyridyloxy(lower)alkyl, phenyl(lower)alkylthio, phenylureido, lower alkoxy(lower)alkoxy, phenyl(lower)alkynyl, dioxothiazolidylidene(lower)alkyl and thienyl optionally substituted by halogen; a naphthyl optionally substituted by halogen; a 4-phenylphenyl substituted by halogen; a thienyl optionally substituted by halogen; a benzothienyl optionally substituted by halogen; a quinolyl optionally substituted by halogen; or a benzooxolanyl optionally substituted by halogen.
Of the above-mentioned compounds, preferred is a compound of the formula (I) wherein R1 is an alkyl, an alkenyl, a phenyl(lower)alkenyl, a phenyl optionally substituted by a substituent selected from the group consisting of alkyl and alkenyl or a thienyl optionally substituted by halogen; A is a heterocyclic group selected from the group consisting of 3H-imidazo[4,5-b]pyridyl, pyrazolo[1,5-a]pyridyl, indolizinyl, 1H-indazolyl, benzo[b]furanyl and benzo[b]thiophenyl, said heterocyclic group being optionally substituted by one or two alkyl; X is an alkylene; and R2 is a phenyl optionally substituted by a substituent selected from the group consisting of alkyl, lower alkoxy, phenyl, halogen, di(lower)alkylamino, lower alkylthio, lower alkoxycarbonyl, nitro, halo(lower)alkyl, phenyl(lower)alkyl, phenyl(lower)alkenyl, phenyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, phenoxy(lower)alkyl, phenyl(lower)alkoxy(lower)alkyl and thienyl optionally substituted by halogen; a naphthyl optionally substituted by halogen; or a 4-phenylphenyl substituted by halogen.
Of the above-mentioned compounds, preferred is a sulfonamide compound (I) wherein A is a 3H-imidazo[4,5-b]pyridyl, a 1H-indazolyl or a benzo[b]furanyl, these heterocyclic groups being optionally substituted by alkyl; and R2 is a phenyl substituted by halogen, said phenyl being optionally substituted by a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, lower alkoxy, phenyl, halogen, di(lower)alkylamino, lower alkylthio, lower alkoxycarbonyl, nitro, halo(lower)alkyl, phenyl(lower)alkyl, phenyl(lower)alkenyl, phenyl(lower)alkoxy, cyclo(lower)alkyl(lower)alkoxy, phenoxy(lower)alkyl, phenyl(lower)alkoxy(lower)alkyl, phenyl(lower)alkynyl and thienyl optionally substituted by halogen, or a naphthyl substituted by halogen, or a salt thereof. Above all a sulfonamide compound (I) wherein A is 3H-imidazo[4,5-b]pyridyl substituted by one or two lower alkyl, 1H-indazolyl substituted by one lower alkyl or benzo[b]Furanyl substituted by one lower alkyl is preferable.
Particularly preferable groups are as follows.
R1: phenyl, 2-nitrophenyl, o- or p-tolyl, n-pentenyl, n-butyl, n-pentyl, n-hexyl, thienyl, 8-quinolyl, (E)-2-phenylethenyl, 4-pentenyl, 4-vinylphenyl, 5-chlorothiophen-2-yl, 5-bromothiophen-2-yl, 4-ethylphenyl,
X: methylene, xe2x80x94OCH2xe2x80x94, oxa
R2: 2,4-dichlorophenyl, 2-chlorophenyl, 4-bromo-2-chlorophenyl, 2,4-dichloro-5-fluorophenyl, 3,4-dichlorophenyl, 2,3-dichlorophenyl, 2,5-dichlorophenyl, 2-bromo-4-chlorophenyl, 4-chloro-2-methoxyphenyl, 4-chloro-2-methylphenyl, 4-phenyl-phenyl, 2-chloro-4-phenylphenyl, 1-bromo-2-naphthyl, 3-chlorobenzo[b]thiophen-2-yl, 2-chloro-4-thiophen-2-yl)phenyl, 2-chloro-4-(5-chlorothiophen-2-yl)phenyl, 2-chloro-4-ethylphenyl, 2-chloro-4-vinylphenyl, 2-chloro-4-methylphenyl, 2-chloro-4-(n-pentyl)phenyl, 2-chloro-4-(i-butyl)phenyl, 2-chloro-4-(cyclohexylmethyl)phenyl, (E)-2-chloro-4-(2-phenylethenyl)phenyl, 4-benzyloxy-2-chlorophenyl, 2-chloro-4-methoxyphenyl, 2-chloro-4-isopropoxyphenyl, 2-chloro-4-(n-butoxy)phenyl, 2-chloro-4-((cyclohexylmethyl)oxy)phenyl, 2-chloro-4-((2-(N-methyl-N-(2-pyridinyl)-amino)ethyl)oxy)phenyl, 2-chloro-4-(methylthio)phenyl, 2-chloro-4-(methylsulfinyl)-phenyl, 2-chloro-4-(methanesulfonyl)phenyl, 4-(benzylamino)-2-chlorophenyl, 4-(n-butylamino)-2-chlorophenyl, 2-chloro-4(N,N-dimethylamino)phenyl, 4-acetylamino-2-chlorophenyl, 2-chloro-4-(methanesulfonylamino)phenyl, 2-chloro-4-nitrophenyl, 2-chloro-4-formylphenyl, 2-chloro-4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-phenyl, 2-chloro-4-fluorophenyl, 2,4,6-trichlorophenyl, 2,3,4-trichlorophenyl, 2-chloro-4-iodophenyl, 2,5-dichlorothiophen-3-yl, 2-chloro-4,5-(methylenedioxy)-phenyl, 2-chloroquinolin-3-yl, 2-chloro-4-(tifluoromethyl)phenyl, 2-chloro-4-cyanophenyl, 2-chloro-4-(2-phenylethyl)phenyl, 2-chloro-4-aminophenyl, 2-chloro-4-(hydroxymethyl)phenyl, 4-carboxy-2chlorophenyl, 2-chloro-4-((methane-sulfonyloxy)methyl)phenyl, 2-chloro-4-((phenyloxy)methyl)phenyl, 2-chloro-4-(ethoxycarbonyl)phenyl, 2-chloro-4-(methylcarbamoyl)phenyl, 2-chloro-4-(dimethyl-aminomethyl)phenyl, 2-chloro-4-((imidazol-1-yl)methyl)phenyl, 2-chloro-4-((piperidin-1-yl)methyl)phenyl, 2-chloro-4-(phenylthiomethyl)phenyl, 4-((benzyloxy)-methyl)-2-chlorophenyl, 4-(benzimidazol-2-yl)-2-chlorophenyl, 4-(1-methylbenz-imidazol-2-yl)-2-chlorophenyl, 1-ethylbenzimidazol-2-yl, 2-chloro-4-(n-pentanethio)-phenyl, 4-(benzylthio)-2-chlorophenyl, 2-chloro-4-((3-pyridyloxy)methyl)phenyl, 2-chloro-4-ethylthiophenyl, 4-(N-butylamino)-2-chlorophenyl, 4-(N-benzoylamino)-2-chlorophenyl, 4-(N-benzoyl-N-methylamino)-2-chlorophenyl, 4-(N-butyryl-N-methyl-amino)-2-chlorophenyl, 2-chloro-4-(N-(n-pentyl)amino)phenyl, 2-chloro-4-(N-methyl-N-(n-pentyl)amino)phenyl, 4-(N-benzenesulfonylamino)-2-chlorophenyl, 2-chloro-4-(isopropoxylcarbonyl)phenyl, 2-chloro-4-(cyclohexyloxycarbonyl)phenyl, 2-chloro-4-(3-phenylureido)phenyl, 2-chloro-4-propoxyphenyl, 2-chloro-4-(n-pentoxy)phenyl, 2-chloro-4-ethoxyphenyl, 2-chloro-4-(2-methoxyethoxy)phenyl, 2-chloro-4-[(thiophen-2-yl)methyloxy]phenyl, 2-chloro-4-[(thiophen-3-yl)methyloxy]phenyl, 2-chloro-4-phenylethynylphenyl, 2-chloro-4-(cyclopentylmethyloxy)phenyl, 2-chloro-4-(1-hexynyl)phenyl, 2-chloro-4-hexylphenyl, 2-chloro-4-piperidinophenyl, 2-chloro-4-morpholinophenyl, 2-chloro-4-(hexamethyleneimino)phenyl, 2-chloro-4-pyrrolidino-phenyl, 2-chloro-4-(4-methylpiperazin-1-yl)phenyl A: 4H-imidazo[1,2-b]pyrazolyl, 3H-thieno[2,3-d]imidazolyl, 1H-thieno[2,3-d]imidazolyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 2,3-dihydrobenzo-[d]imidazolyl, 1H-indazolyl, indolizinyl, benzotriazolyl, 1H-imidazo[4,5-b]pyridyl, 3H-imidazo[4,5-b]pyridyl, pyrrolo[1,5-a]pyridyl, benzo[b]furanyl, benzo[b]thiophenyl, 3,4-dihydroquinazolinyl, 1,2-dihydroquinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, quinolyl, 1,2,3,4-tetrahydroquinazolinyl, 1,4-dihydroquinazolinyl, 2H-indazolyl Substitutent of A: methyl, ethyl, n-propyl, oxo
Preferred objective compounds (I) are as follows.
3-(3,4-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(2,3-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(2,5-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(2,4-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)pyrazolo[1,5-a]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(benzenesulfonylcarbamoyl)pyrazolo[1,5-a]pyridine
1-(2,4-dichlorobenzyl)-2-methyl-7-(n-pentanesulfonylcarbamoyl)indolizine
7-n-butanesulfonylcarbamoyl-1-(2,4-dichlorobenzyl)-2-methylindolizine
1-(2,4-dichlorobenzyl)-1-methyl-7-(benzenesulfonylcarbamoyl)indolizine
2-methyl-7-(n-pentanesulfonylcarbamoyl)-1-(4-phenylbenzyl)indolizine
6-(n-pentanesulfonylcarbamoyl)-4-(4-phenylbenzyl)quinoline
3-(2,4-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(n-butanesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-benzenesulfonylcarbamoyl-3-(2,4-chlorobenzyl-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(1-bromo-2-naphthyl)methyl-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
2-methyl-5-(n-pentanesulfonylcarbamoyl)-3-(4-phenylbenzyl)-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-5-(n-butanesulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-bromo-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-bromo-4-chlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-bromo-4-chlorobenzyl)-2-methyl-3H-imidazo)[4,5-b]pyridine
3-(2-bromo-4-chlorobenzyl)-5-(n-butanesulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-6-(n-pentanesulfonylcarbamoyl)indolizine
3-(2,4-dichlorobenzyl)-2-methyl-6-(n-butanesulfonylcarbamoyl)indolizine
3-(2,4-dichlorobenzyl)-2-methyl-6-(benzenesulfonylcarbamoyl)indolizine
3-(2,4-dichlorobenzyl)-2-ethyl-7-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
2-ethyl-7-methyl-5-(n-pentanesulfonylcarbamoyl)-3-(4-phenylbenzyl)-3H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(benzenesulfonylcarbamoyl)benzo[b]thiophene
3-(2,4-dichlorobenzyl)-2-methyl-5-(n-butanesulfonylcarbamoyl)benzo[b]thiophene
3-(4-phenylbenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(2-chlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(4-bromo-2-chlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-benzo[b]thiophene
3-(2,4-dichloro-5-fluorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-benzo[b]thiophene
3-((3-chlorobenzo[b]thiophen-2-yl)methyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
3-(1-bromonaphthalen-2-yl)methyl-2-methyl-5-(n-pentanesulfonylcarbamoyl)benzo[b]thiophene
1-(2,4-dichlorobenzyl)-2-methyl-5-n-pentanesulfonylcarbamoyl-1H-thieno[2,3-d]imidazole
3-(2,4-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-thieno[2,3-d]imidazole
1-(2,4-dichlorobenzyl)-2-methyl-6-(n-pentanesulfonylcarbamoyl)-1H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)pyrrolo[3,2-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(benzenesulfonylcarbamoyl)pyrrolo[3,2-b]pyridine
3-(4-chloro-2-methoxybenzyl-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-chloro-2-methylbenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-benzenesulfonylcarbamoyl-3-(4-chloro-2-methyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-benzenesulfonylcarbamoyl-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(n-butanesulfonylcarbamoyl)-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(1-n-pentanesulfonylcarbamoyl)benzo[b]furan
5-(benzenesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methylbenzo[b]furan
2-(2,4-dichlorobenzyl)-3,5-dimethyl-7-(1-n-pentanesulfonylcarbamoyl)benzo[b]furan
7-(benzenesulfonylcarbamoyl)-2-(2,4-dichlorobenzyl)-3,5-dimethylbenzo[b]furan
2-methyl-5-(1-n-pentanesulfonylcarbamoyl)-3-(4-phenylbenzyl)benzo[b]furan
5-(1-benzenesulfonylcarbamoyl)-2-methyl-3-(4-phenylbenzyl)benzo[b]furan
5-(1-n-butanesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methylbenzo[b]furan
3-(2,4-dichlorobenzyl)-5-(1-n-hexanesulfonylcarbamoyl)-2-methylbenzo[b]furan
3-(2,4-dichlorobenzyl)-2-methyl-5-(2-thiophenesulfonylcarbamoyl)benzo[b]furan
3-(2,4-dichlorobenzyl)-2-ethyl-5-(1-n-pentanesulfonylcarbamoyl)benzo[b]furan
5-(benzenesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-ethylbenzo[b]furan
3-(2,4-dichlorobenzyl)-2-ethyl-5-(8-quinolinesulfonylcarbamoyl)benzo[b]furan
3-(2,4-dichlorobenzyl)-2-ethyl-5-((2-methylbenzene)sulfonylcarbamoyl)-benzo[b]furan
3-(2,4-dichlorobenzyl)-5-(1-n-pentanesulfonylcarbamoyl)-2-propylbenzo[b]furan
5-(benzenesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-propylbenzo[b]furan
b 3-(2,4-dichlorobenzyl)-5-ethyl-(2-nitrobenzenesulfonylcarbamoyl)-2-propylbenzo[b]furan
3-(2,4-dichlorobenzyl)-5-(1-n-pentanesulfonylcarbamoyl)benzo[b]furan
3-(2,4-dichlorobenzyl)-2-methyl-5-(1-n-pentanesulfonylcarbamoyl)-benzo[b]thiophene
2-(2,4-dichlorobenzyl)-3-ethyl-7-(1-n-pentanesulfonylcarbamoyl)benzo[b]thiophene
7-(benzenesulfonylcarbamoyl)-2-(2,4-dichlorobenzyl)-3-ethylbenzo[b]thiophene
6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-2-benzimidazolone
1-(2,4-dichlorobenzyl)-3-methyl-6-(1-pentanesulfonylcarbamoyl)-1H-indazole
6-(benzenesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-1H-indazole
(E)-1-(2,4-dichlorobenzyl)-3-methyl-6-((2-phenylethenyl)sulfonylcarbamoyl)-1H-indazole
6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)benzotriazole
6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)benzotriazole
6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-1H-indazole
7-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-4(3H)-quinazolinone
7-(1-n-butanesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-1-methyl-4(3H)-quinazolinone
7-(1-n-butanesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-4(3H)-quinazolinone
7-(1-n-butanesulfonylcarbamoyl)-2-(2,4-dichlorobenzyl)-3-methyl-4(3H)-quinazolinone
6-(1-n-butanesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-3,4-dihydro-2-methylquinazoline,hydrochloride
1-(2,4chlorobenzyl)-2-methyl-7-(1-n-pentanesulfonylcarbamoyl)-4(1H)-quinazolinone
7-(benzenesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-2-methyl-4(1H)-quinazolinone
1-(2,4-dichlorobenzyl)-1,4-dihydro-2-methyl-7-(1-n-pentanesulfonylcarbamoyl)quinazoline,hydrochloride
7-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-2(1H)-quinoxalinone
7-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-4-methyl-2,3-(1H,4H)-quinoxalinedione
4-(2,4-dichlorobenzyl)-5-ethyl-3-(1-n-pentanesulfonylcarbamoyl)imidazo[1,2-b]pyrazole
3-(2,4-dichlorobenzyl)-2-methyl-6-(1-n-pentanesulfonylcarbamoyl)imidazo[1,2-a]pyridine
6-(n-pentanesulfonylcarbamoyl)-4-(4-phenylphenyloxy)quinoline
6-(n-pentanesulfonylcarbamoyl)-4-(4-phenylbenzyloxy)quinoline
3-(2,4-dichlorobenzyl)-2-ethyl-5-(((E)-pentene-1-sulfonyl)carbamoyl)benzo[b]furan
1-(2,4-dichlorobenzyl)-3-ethyl-6-(1-n-pentanesulfonylcarbamoyl)-1H-indazole
6-(benzenesulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-3-ethyl-1H-indazole
6-(benzenesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-2-methylimidazo[1,2-a]pyridine
3-(2,3-dichlorobenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-((3-chlorobenzo[b]thiophen-2-yl)methyl)-2-methyl-5-n-pentanesulfonyl-carbamoyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-(n-pentanesulfonylcarbamoyl)-benzo[b]thiophene
3-(2chloro-4-phenylbenzyl)-2-methyl-5-(((E)-1-pentene-1-sulfonyl)carbamoyl)-3H-imidazo[4,5-b]pyridine
1-(2-chloro-4-phenylbenzyl)-3-methyl-6-(1-pentanesulfonylcarbamoyl)-1H-indazole
6-(benzenesulfonylcarbamoyl)-1-(2-chloro-4-phenylbenzyl)-3-methyl-1H-indazole
(E)-1-(2-chloro-4-phenylbenzyl)-3-methyl-6-((2-phenylethenyl)sulfonylcarbamoyl)-1H-indazole
1-(2-chloro-4-phenylbenzyl)-3-methyl-6-(((E)-1-pentene-1-sulfonyl)carbamoyl)-1H-indazole
1-(2-chloro-4-phenylbenzyl)-3-methyl-6-((4-vinylbenzene)sulfonylcarbamoyl-1H-indazole
1-(2-chloro-4-phenylbenzyl)-3-methyl-6-((4-methylbenzene)sulfonylcarbamoyl)-1H-indazole
1-(4-bromo-2-chlorobenzyl)-3-methyl-6-(1-pentanesulfonylcarbamoyl)-1H-indazole
6-(benzenesulfonylcarbamoyl)-1-(4-bromo-2-chlorobenzyl)-3-methyl-1H-indazole
(E)-1-(4-bromo-2-chlorobenzyl)-3-methyl-6-((2-phenylethenyl)sulfonylcarbamoyl-1H-indazole
3-(2,4-dichlorobenzyl)-2-methyl-5-(((E)-1-pentene-1-sulfonyl)carbamoyl)-benzo[b]furan
(E)-3-(2,4-dichlorobenzyl)-2-methyl-5-((2-phenylethenyl)sulfonylcarbamoyl)-benzo[b]furan
3-(2,4-dichlorobenzyl)-2-methyl-5-((4-vinylbenzene)sulfonylcarbamoyl)-benzo[b]furan
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-benzo[b]furan
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-phenylbenzyl)-2-methylbenzo[b]furan
(E)-3-(2-chloro-4-phenylbenzyl)-2-methyl-5-((2-phenylethenyl)sulfonyl-carbamoyl)benzo[b]furan
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-(4-vinylbenzenesulfonylcarbamoyl)-benzo[b]furan
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-(((E)-1-pentene-1-sulfonyl)carbamoyl)-benzo[b]furan
3-(4-bromo-2-chlorobenzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-benzo[b[furan
5-(benzenesulfonylcarbamoyl)-3-(4-bromo-2-chlorobenzyl)-2-methylbenzo[b]furan
(E)-3-(4-bromo-2-chlorobenzyl)-2-methyl-5-((2-phenylethenyl)sulfonylcarbamoyl)-benzo[b]furan
3-(2,4-dichlorobenzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
(E)-3-(2,4-chlorobenzyl)-2-methyl-5-[(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
(E)-3-(4-bromo-2-chlorobenzyl)-2-methyl-5-[(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
(E)-3-(2-chloro-4-phenylbenzyl)-2-methyl-5-[(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-5-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-5-[(4-ethylbenzene)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-[2-chloro-4-(thiophen-2-yl)benzyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-[2-chloro-4-(5-chlorothiophen-2-yl)benzyl]-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethylbenzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-ethylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethylbenzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
(E)-3-(2-chloro-4-ethylbenzyl)-2-methyl-5-[(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-vinylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-methylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(n-pentyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-isobutylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(cyclohexylmethyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
(E)-5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(2-phenylethenyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-benzyloxy-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-methoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-isopropoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-(n-butoxy)-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcabamoyl)-3-(2-chloro-4-((2-(N-methyl-N-(2-pyridinyl)amino)ethyl)oxy)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(methythio)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(methylsulfinyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(methanesulfonyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-(benzylamino)-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-(n-butylamino)-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(N,N-dimethylamino)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(4-(acetamide)-2-chlorobenzyl)-5-(benzenesulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(methanesulfonylamino)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-nitrobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-formylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-[2-chloro-4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]benzyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-fluorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-2-methyl-3-(2,4,6-trichlorobenzyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-2-methyl-3-(2,3,4-trichlorobenzyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2,4-dichloro-5-fluorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-iodobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-((2,5-dichlorothiophen-3-yl)methyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4,5-(methylenedioxy)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-((2-chloroquinolin-3-yl)methyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(tifluoromethyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(trifluoromethyl)benzyl]-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(trifluoromethyl)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(1-bromonaphthalen-2-ylmethyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-5-(pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
(E)-3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-5-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-5-((4-vinylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(1-bromonaphthalen-2-ylmethyl)-2,7-dimethyl-5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
(E)-3-(4-bromo-2-chlorobenzyl)-2,7-dimethyl-5-[(2-phenylethenyl)sulfonyl-carbamoyl]-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-5-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-2,7-dimethyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(4-bromo-2-chlorobenzyl)-5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-nitrobenzyl)-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-nitrobenzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
(E)-3-(2-chloro-4-nitrobenzyl)-2,7-dimethyl-5-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-nitrobenzyl)-2,7-dimethyl-5-((4-vinylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-cyanobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
(E)-3-(2-chloro-4-(trifluoromethyl)benzyl)-2-methyl-5-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(trifluoromethyl)benzyl)-2-methyl-5-((4-vinylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(trifluoromethyl)benzyl)-5-((5-chlorothiophen-2-yl)sulfonyl-carbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(2-chloro-4-(trifluoromethyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-phenylbenzyl)-2-methylbenzo-[b]thiophene
1-(2-chloro-4-phenylbenzyl)-6-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-3-methyl-1H-indazole
6-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-1-(2-chloro-4-phenylbenzyl)-3-methyl-1H-indazole
3-(1-bromonaphthalen-2-ylmethyl)-5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(2-phenylethyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(4-amino2-chlorobenzyl)-5-(benzenesulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(hydroxymethyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(4-carboxy-2-chlorobenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-((methanesulfonyloxy)methyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(ethoxycarbonyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-(methylcarbamoyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(E)-(2-phenylethenyl)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(E)-(2-phenylethenyl)benzyl)-2-methyl-5-((4-vinylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(E)-(2-phenylethenyl)benzyl)-2-methyl-5-(E)-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(E)-(2-phenylethenyl)benzyl)-5-((5-chlorothiophen-2-yl)sulfonyl-carbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(E)-(2-chloro-4-(2-phenylethenyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(E)-(2-phenylethenyl)benzyl)-2-methyl-5-(1-pentanesulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(2-phenylethyl)benzyl)-2-methyl-5-((4-methylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(2-phenylethyl)benzyl)-2-methyl-5-((4-vinylbenzene)sulfonyl-carbamoyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(2-phenylethyl)benzyl)-2-methyl-5-(E)-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(2-phenylethyl)benzyl)-5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(2-chloro-4-(2-phenylethylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(2-phenylethyl)benzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-2-methyl-5-((4-vinylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-2-methyl-5-(E)-((2-phenylethenyl)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(4-benzyloxy-2-chlorobenzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-5-((4-methylbenzene)-sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-5-((4-vinylbenzene)-sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-5-(E)-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((cyclohexylmethyl)oxy)benzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(methylthio)benzyl)-2-methyl-5-[(4-methylbenzene)-sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(methylthio)benzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(methylthio)benzyl)-2-methyl-5-(E)-(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(methylthio)benzyl)-5-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(methylthio)benzyl]-5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2chloro-4-(methylthio)benzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(ethoxycarbonyl)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(ethoxycarbonylbenzyl)-2-methyl-5-((4-vinylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(ethoxycarbonyl)benzyl)-2-methyl-5-(E)-((2-phenylethenyl)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(ethoxycarbonyl)benzyl)-5-((5-chlorothiophen-2-yl)sulfonyl-carbamoyl)-2-methyl-3H-imidazo[4,5-b]pyridine
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl-3-(2-chloro-4-(ethoxycarbonyl)-benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(ethoxycarbonyl)benzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-5-[(E)-(2-phenyletheny)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((phenyloxy)methyl)benzyl)-5-[(5-chlorothiophen-2-yl)sulfonyl-carbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((phenyloxy)methyl)benzyl)-2-methyl-5-(1-pentanesulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(dimethylaminomethyl)benzyl]-2-methyl-5-[(4-methylbenzene)-sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-((imidazol-1-yl)methyl)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-((piperidin-1-yl)methyl)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(phenylthiomethyl)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(4-((benzyloxy)methyl)-2-chlorobenzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[4-(benzimidazol-2-yl)-2-chlorobenzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3-[4-(1-methylbenzimidazol-2-yl)-2-chlorobenzyl]-3H-imidazo[4,5-b]pyridine
3-[(1-ethylbenzimidazol-2-yl)methyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(thiophen-2-yl)benzyl)-2-methyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(thiophen-2-yl)benzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(thiophen-2-yl)benzyl)-5-[(5chlorothiophen-2-yl)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-(thiophen-2-yl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2chloro-4-(thiophen-2-yl)benzyl)-2-methyl-5-[(E)-(2-phenylethene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(thiophen-2-yl)benzyl)-2-methyl-5-[(4-vinylbenzene)sulfonyl-carbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(5-chlorothiophen-2-yl)benzyl)-2-methyl-5-(1-pentanesulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(5-chlorothiophen-2-yl)benzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(5-chlorothiophen-2-yl)benzyl)-5-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2-methyl-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-(5-chlorothiophen-2-yl)benzyl)-2-methyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(5-chlorothiophen-2-yl)benzyl)-2-methyl-5-[(E)-(2-phenylethene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2chloro-4-(5-chlorothiophen-2-yl)benzyl)-2-methyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-5-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-phenylbenzyl)-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylbenzyl)-2,7-dimethyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(thiophen-2-yl)benzyl]-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(thiophen-2-yl)benzyl]-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-[2-chloro-4-(thiophen-2-yl)benzyl]-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(thiophen-2-yl)benzyl]-2,7-dimethyl-5-[(E)-(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(thiophen-2-yl)benzyl]-2,7-dimethyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(5chlorothiophen-2-yl)benzyl]-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(5chlorothiophen-2-yl)benzyl]-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-[2-chloro-4-(5-chlorothiophen-2-yl)benzyl]-2,7-dimethyl-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(5-chlorothiophen-2-yl)benzyl]-2,7-dimethyl-5-[(E)-(2-phenylethenyl)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(5-chlorothiophen-2-yl)benzyl]-2,7-dimethyl-5-[(4-vinylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(n-pentanethio)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[4-(benzylthio)-2chloro]benzyl-2-methyl-5-[(4-methylbenzene)sulfonyl-carbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-((3-pyridyloxy)methyl)benzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethylthiobenzyl)-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(4-(N-butyrylamino)-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-(N-benzoylamino)-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-(N-benzoyl-N-methylamino)-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
5-(benzenesulfonylcarbamoyl)-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine sodium salt
5-[(4-vinylbenzene)sulfonylcarbamoyl]-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine sodium salt
5-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]-3-(2-chloro-4-phenylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine sodium salt
3-(4-bromo-2-chlorobenzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine sodium salt
3-(4-(N-butyryl-N-methylamino)-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(N-(n-pentyl)amino)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(N-methyl-N-(n-pentyl)amino)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(4-(N-benzenesulfonylamino)-2-chlorobenzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(isopropoxylcarbonyl)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(cyclohexloxycarbonyl)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(3-phenylureido)benzyl)-2-methyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-propoxybenzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(n-pentoxy)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonyl-carbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethoxy)benzyl-2-methyl-5-[(4-methylbenzene)sulfonylcarbarmoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(2-methoxyethoxy)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-[(thiophen-2-yl)methyloxy]benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-[(thiophene-3-yl)methyloxy]benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylethynyl)benzyl-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-[2-chloro-4-(cyclopentylmethyloxy)benzyl]-2-methyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-phenylethynyl)benzyl-2,7-dimethyl-5-(1-pentanesulfonylcarbarmoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(1-hexynyl)benzyl-2-methyl-5-(N-(4-methylphenyisulfonyl)carbamoyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(cyclohexylmethyloxy)benzyl)-2,7-dimethyl-5-((1-pentanesulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(cyclohexylmethyloxy)benzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethylbenzyl)-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethylbenzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(trifluoromethyl)benzyl)-2,7-dimethyl-5-(1-pentanesulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(trifluoromethyl)benzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethoxybenzyl)-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-ethoxybenzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonylcarbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2,4-dichlorobenzyl)-2-methyl-5-(p-toluenesulfonylcarbamoyl)benzo[b]furan
5-((5-bromothiophen-2-yl)sulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methylbenzo[b]furan
5-((5-chlorothiophen-2-yl)sulfonylcarbamoyl)-3-(2,4-dichlorobenzyl)-2-methylbenzo[b]furan
3-(2-chloro-4-phenylbenzyl)-2-methyl-5-((4-pentene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
2-(2-chloro-4-phenylbenzyl)-3-methyl-6-(p-toluenesulfonylcarbamoyl)-2H-indazole
3-(2-chloro-4-hexylbenzyl)-2-methyl-5-(N-(4-methylphenylsulfonyl)carbamoyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-pipedinobenzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-morpholinobenzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonyl-carbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(hexamethyleneimino)benzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonylcarbamoyl-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(1-pyrrolidinyl)benzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-(4-methylpiperazin-1-yl)benzyl)-2,7-dimethyl-5-((4-methylbenzene)sulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-methylthiobenzyl)-2,7-dimethyl-5-[(4-methylbenzene)sulfonyl-carbamoyl]-3H-imidazo[4,5-b]pyridine
3-(2-chloro-4-methylthiobenzyl)-2,7-dimethyl-5-(1-pentanesulfonylcarbamoyl)-3H-imidazo[4,5-b]pyridine
The methods for producing the objective compound (I) are described in detail in the following.
Production Method 1
The objective compound (I) and a salt thereof can be produced by reacting compound (II) or a salt thereof with compound (III) or a reactive derivative thereof at its carboxy group or a salt thereof.
The compound (II), compound (III) and reactive derivative at carboxyl group thereof are exemplified by those shown with regard to compound (I).
Preferable reactive derivative at carboxy of compound (III) is acid halide, acid anhydride such as intramolecular add anhydride, intermolecular acid anhydride and mixed acid anhydride, active amide, active ester and the like. Preferable examples thereof include acid chloride, acid azide, mixed acid anhydride with acid such as substituted phosphoric acid (e.g., dialkylphosphinic acid, phenylphosphonic acid, diphenylphosphinic acid, dibenzylphosphinic acid and halogenated phosphoric add), dialkylphosphinic acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid (e.g., methanesulfonic acid), aliphatic carboxylic acid (e.g., acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid and trichloroacetic acid), aromatic carboxylic acid (e.g., benzoic acid), and the like; symmetric acid anhydride; active amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; active ester (e.g., cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl [(CH3)2N+xe2x95x90CHxe2x80x94] ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthio ester, p-nitrophenylthio ester, p-cresylthio ester, carboxymethylthio ester, pyranyl ester, pyridyl ester, piperidyl ester and 8-quinolylthio ester); esters with N-hydroxy compound (e.g., N,N-dimethylhydroxylamine, 1-hydroxy-2-1H-pyridone, N-hydroxysuccinimide and 1-hydroxy-1H-benzotriazole); and the like. These reactive derivatives can be appropriately selected according to the kind of compound (III) to be used.
The reaction generally proceeds in a conventional solvent such as water, alcohol (e.g., methanol and ethanol), acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide and pyridine, or in a solvent which does not adversely affect the reaction. These conventional solvents may be used alone or in combination.
When compound (III) is used in the form of a free acid or a salt thereof in this reaction, the reaction is preferably carried out in a conventional condensing agent such as N,Nxe2x80x2-dicyclohexylcarbodiimide, N-cyclohexyl-Nxe2x80x2-morpholinoethyl-carbodiimide, N-cyclohexyl-Nxe2x80x2-(4-diethylaminocyclohexyl)-carbodiimide, N,Nxe2x80x2-diethylcarbodiimide, N,Nxe2x80x2-diisopropylcarbodiimide, N-ethyl-Nxe2x80x2-(3-dimethylamino-propyl)carbodiimide, N,Nxe2x80x2-carbonylbis(2-methylimidazole), pentamethyleneketen-N- cyclohexylimine, diphenylketen-N-cyclohexylimine, ethoxyacetylene, 1-alkoxy-1-chloroethylene, trialkyl phosphite, ethyl polyphosphorate, isopropyl polyphosphorate, phosphorous oxychloride (phosphoryl chloride), phosphorous trichloride, diphenylphosphoryl azide, diphenyl chlorophosphate, diphenylphosphinic acid chloride, thionyl chloride, oxalyl chloride, lower alkyl haloformate (e.g., methyl chloroformate and isopropyl chloroformate), triphenylphosphine, 2-ethyl-7-hydroxybenzoisoxazolium salt, intramolecular salt of 2-ethyl-5(m-sulfophenyl)isoxazolium hydroxide, 1-(p-chlorobenzensulfonyloxy)-6-chloro-1H-benzotriazole, and so called Vilsmeier reagent(prepared from N,N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, or phosphoryl chloride, and so on.), and the like.
The reaction can be carried out in the presence of an inorganic or organic base such as alkali metal bicarbonate, tri(lower)alkylamine, pyridine, 4-dimethyl-aminopyridine, N-lower)alkylmorpholine, N,N-di(lower)alkylaniline (e.g., N,N-dimethylaniline), N,N-di(lower)alkylbenzylamine, and the like.
The reaction temperature is not particularly limited, and the reaction is generally carried out from under cooling to heating.
Production Method 2
The objective compound (I-2) and a salt thereof can be prepared by reducing compound (I-1) or a salt thereof.
The method for producing objective compound (I-2) by reduction includes chemical reduction and catalytic reduction.
The preferable reducing agent used in the chemical reduction is, for example, metal such as tin, zinc and iron, or a combination of a metal compound, such as chromium chloride and chromium acetate, and an organic acid or inorganic acid such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid and hydrobromic acid.
The preferable reducing agent used in the catalytic reduction is, for example, platinum catalyst such as platinum plate, platinum sponge, platinum black, platinum colloid, platinum oxide and platinum wire, palladium catalyst such as palladium sponge, palladium black palladium oxide, palladium carbon, palladium colloid, palladium-barium sulfite and palladium-barium carbonate, nickel catalyst such as reduced nickel and Raney-nickel, cobalt catalyst such as reduced cobalt and Raney cobalt, iron catalyst such as reduced iron and Raney iron, copper catalyst such as reduced copper, Raney copper and Ullmann copper, and the like.
The reducion is generally carried out in a conventional solvent that does not adversely influence the reaction, such as water, methanol, ethanol, propanol and N,N-dimethylformamide, or a mixed solvent thereof. When the above-mentioned acid to be used for the chemical reduction is liquid, it can be used as a solvent.
The preferable solvent to be used for the catalytic reduction includes, besides the above-mentioned solvents, other conventional solvents such as diethyl ether, dioxane and tetrahydrofuran and mixtures thereof.
The reaction temperature of the reduction is not particularly limited, and the reaction is generally carried out from under cooling to heating.
Production Method 3
The objective compound (I-4) and a salt thereof can be produced by oxidizing compound (I-3) or a salt thereof.
When objective compound (I4) is produced by oxidation, an oxidizing agent such as sodium chlorite, chromic anhydride and potassium permanganate, and a solvent such as water and acetone are used. The reaction temperature is not particularly limited, and the reaction is generally carried out from under cooling to heating.
Production Method 4
The objective compound (I-6) and a salt thereof can be produced by acylation of compound (I-5) or a salt thereof.
When objective compound (I-6) is to be obtained by acylation, compound (I-5) having terminal hydroxy is reacted with an acylating agent Examples of the acylating agent include lower alkanesulfonyl halide (e.g., methanesulfonyl chloride) and lower alkanesulfonic anhydride (e.g., methanesulfonic anhydride). The solvent may be dichloromethane, tetrahydrofuran and the like, and the reaction proceeds from under from ice-cooling to heating.
Production Method 5
The objective compound (I-7) and a salt thereof can be produced by introducing an aryloxy group into compound (I-6) or a salt thereof. For the introduction of the aryloxy group, compound (I-6) having terminal acyloxy(lower)alkyl is reacted with hydroxyaryl compound (e.g., phenol) in the presence of a base such as sodium hydride. As the solvent, N,N-dimethylformamide, tetrahydrofuran and the like can be used, and the reaction proceeds from under ice-cooling to heating.
Production Method 6
The objective compound (I-8) and a salt thereof can be produced by introducing a carboxy-protecting group into compound (I-4) or a reactive derivative thereof.
The carboxy-protecting group can be introduced by, for example, reacting compound (I4) having terminal carboxyl or a reactive derivative thereof with an alkyl alcohol such as ethanol. As the solvent, N,N-dimethylformamide, dichloromethane and the like can be used, and the reaction proceeds from under ice-cooling to heating.
The preferable reactive derivative at carboxy includes acid halide, acid anhydride, active amide, active ester and the like. Preferable examples thereof are acid chrolide, acid azide, mixed acid anhydride with acid such as substituted phosphoric acid (e.g., dialkyl phosphoric acid, phenylphosphonic acid, diphenyl-phosphinic add, dibenzylphosphinic add and halogenated phosphoric add), dialkylphosphinic acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid (e.g., methanesulfonic acid), aliphatic carboxylic acid (e.g., acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid and trichloroacetic acid), aromatic carboxylic acid (e.g., benzoic acid), and the like; symmetric acid anhydride; active amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; active ester (e.g., cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl [(CH3)2N+xe2x95x90CHxe2x80x94] ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthio ester, p-nitrophenylthio ester, p-cresylthio ester, carboxymethylthio ester, pyranyl ester, pyridyl ester, piperidyl ester and 8-quinolyl ester, esters with N-hydroxy compound (e.g., N,N-dimethylhydroxylamine, 1-hydroxy-2-1H-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide and 1-hydroxy-1H-benzotriazole), and the like. These reactive derivatives can be selected according to the kind of compound to be used.
Production Method 7
The objective compound (I-9) and a salt thereof can be produced by introducing a carboxy-protecting group into compound (I-4) or a salt thereof.
When compound (I-4) is reacted with alkylamine such as methylamine and ethylamine, this compound is amidated. The solvent to be used is, for example, tetrahydrofuran, dichloromethane, N,N-dimethylformamide and the like, and the reaction proceeds from under ice-cooling to heating.
Production Method 8
The objective compound (I-11) and a salt thereof can be produced by adding a heterocyclic group containing nitrogen to compound (I-10) or a salt thereof.
This reaction is preferably carried out in the presence of a base such as sodium tert-butylate and the above-mentioned inorganic or organic base. The reaction is preferably carried out in the presence of a catalyst such as tris(dibenzylideneacetone)-dipalladium(O), (R)-(+)-BINAP [2,2xe2x80x2-bis(diphenyl-phosphino)-1,1xe2x80x2-binaphthyl] and the like.
While the reaction temperature is not particularly limited, the reaction is carried out from room temperature to heating, and the reaction can be also carried out in the presence of a solvent such as toluene, which does not adversely affect the reaction.
The above-mentioned compounds can be purified as necessary according to a conventional method for purifying an organic compound, such as recrystallization, column chromatography, thin-layer chromatography, high performance liquid chromatography and the like. The compound can be identified by NMR spectrometric analysis, mass spectrometric analysis, IR spectrometric analysis, elemental analysis, melting point measurement and the like.
The compound of the present invention may have one or more chiral centers and includes enantiomers and diastereomers. Some compounds having alkenyl may be present as a cis or trans isomer. The present invention encompasses such mixtures and respective isomers.
The inventive compound and a salt thereof may be in the form of a solvate, which is also encompassed in the present invention. The solvate is preferably exemplified by hydrate and ethanolate.
The pharmaceutical data of compound (I) are shown in the following to demonstrate the utility of the objective compound (I).
(blood sugar level depressing activity in dd/db mice)
Test Compound
Compound A
3-(2,4-Dichlorobenzyl)-2-methyl-5-(1-n-pentanesulfonylcarbamoyl)-benzo[b]furan (compound of Example 30-1)
Test Animal
Female C57BL/KsJ-dbm db+/db+, C57BL/KsJ-dbm +m/+m (Jackson Laboratory) mice (5 weeks old) were purchased and subjected to the test after 2-3 weeks of acclimating period.
Drug Administration
The test drug was mixed with a powder diet (CE-2, Clea Japan, Inc.) in a mortar. In the case of administration in 100 mg/kg, the mixing proportion of the test drug to the diet was 0.1%, in the case of 30 mg/kg, the proportion was 0.03% and in the case of 10 mg/kg, the proportion was 0.01%. The diet was changed twice a week. The amount of the diet given and the amount left were recorded and the diet intake was calculated by determining the difference.
Test Schedule
The female db/db mice were grouped according to body weight, blood sugar level and triglceride concentration in blood. Then, the drug-mixed diet was given for 14 days, during which period the mice were 8 to 10 weeks of age. At day 7 and day 14 in the morning, blood was taken from supraorbital plexus venosus using a heparinized glass capillary tube (Chase Heparinized capillary tube), and centrifuged to give plasma fractions. The blood sugar value, triglyceride concentration in plasma and insulin concentration in plasma were measured at day 0 and day 14, and blood sugar value and triglyceride concentration in blood were measured at day 7. Body weight was measured at day 0, day 7 and day 14. After final blood sampling, the mice were slaughtered with CO2 gas.
Measurement Method
Blood sugar value was measured using 10-15 xcexcl of plasma and in accord with glucose oxidase method glucose CII-test Waco, Waco Pure Chemicals Co., Ltd.). The triglyceride concentration in plasma was measured using 10-15 xcexcl of plasma and in accord with GPO-p chlorophenol method (triglyceride G-test Waco) or GPO-DAOS method (triglyceride E-test Waco). The measurement was done promptly after blood sampling. The insulin concentration in plasma was measured using 20 xcexcl of plasma (preservable at xe2x88x9220xc2x0 C.) and in accord with an antibody method (Phadesef Insulin RIA kit, Kabi Pharmacia).
Result
Using the difference between db/db mice control group and +/+ mice in blood sugar value and triglyceride concentration in plasma as 100%, the proportion (%) of decrease in the blood sugar value and triglyceride concentration in plasma of the group administered with the test drug was determined. The results are shown in Table 1.
The compound (I) of the present invention can be used for therapeutic purposes in the form of a pharmaceutical preparation. This pharmaceutical preparation contains any one of the compounds (I) as an active ingredient in admixture with a pharmaceutically acceptable organic or inorganic excipient which is a solid, semi-solid or liquid and which is suitable for oral, parenteral or external (local) administration. Examples of the dosage form include capsules, tablets, sugar coating tablets, granules, suppositories, liquid, lotion, suspension, emulsion, ointment, gel and the like. When desired, these preparations may contain adjuvant auxiliary, auxiliary substance, stabilizer, moistening agent, emulsifier, buffering agent, and other conventional additives.
While the dose of the compound (I) varies depending on the age and symptom of patients, compound (I) is administered for the therapy of the above-mentioned diseases in an average single dose amount of about 0.1 mg, 1 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg or 1000 mg. In general, its daily dose is about 0.1 mg/patient to about 1000 mg/patient.